The physical and chemical nature of the principal pathway(s) for water and hydrophilic solutes across the capillary wall remains poorly understood. The specific aims of the proposed research are to investigate two hypotheses describing mechanisms of water flow and solute diffusion and exclusion in the transcapillary pathways. One states that a network of fibrous molecules on the endothelial cell surface is the principal determinant of the permeability and selectivity of the capillary wall. The second hypothesis states that the plasma proteins interact with the fiber matrix to maintain the normal permeability properties of the capillary wall. To test these hypotheses we will use methods developed in our laboratory to measure the permeability properties of the walls of individually perfused capillary blood vessels. The hydraulic conductivity will be measured using a modified Landis microocclusion technique. A microscope photometer will be used to measure the permeability coefficients to colored hydrophilic solutes with molecular weights between 2000 and 20,000 and a range of shape and charge of physiological pH. We will seek an internally consistent description of the measured permeability properties in terms of the fiber radius and volume of a fiber matrix within the transcapillary pathways. The investigations provide a direct experimental route to further understanding of the mechanisms which maintain, and possibly regulate, vascular permeability. They will also lead towards a better understanding of the relation between changes in blook composition and abnormalities of vascular wall structure.